Method for controlling the growth of microorganisms



United States Patent Otfice 3,525,792- Patented Aug. 25, 1970 Int. Cl.A01u 9/00 US. Cl. 424-288 11 Claims ABSTRACT OF THE DISCLOSURE Inaccordance with certain of its aspects, the method of this invention forcontrolling the growth of microorganisms which comprises applying to thelocus at which control is desired a compound of the formula wherein R isa hydrocarbon radical selected from the group consisting of lower alkylradicals and the phenyl radical; a, b, x, and y, are selected from thegroup consisting of O and 1; a+b=1; and x+y=1.

This invention relates to tin-containing derivatives of sulfosalicylicacid and to methods of preparing the same.

This is a divisional application of Ser. No. 159,738, filed Dec. 15,1961, now Patent No. 3,201,432.

It is an object of this application to set forth novel compositions ofmatter particularly characterized by their unexpectedly high meltingpoint and by their activity against microorganisms. It is a furtherobject to set forth a technique of preparing these novel compositions.Other objects will be apparent to those skilled in the art on inspectionof the following description.

In accordance with certain of its aspects, the novel process of thisinvention comprises the steps of mixing together sulfosalicylic acidhaving the formula with (l-i-x/Z) moles of (R Sn) O for each mole ofsaid acid, and heating said mixture thereby completing reaction to formLOOSnRa wherein a, b, x, and y are each independently selected from thegroup consisting of 0 and 1; wherein a+b=1; and x+y= l.

Sulfosalicylic acid may be commercially available as3carboxy-4hydroxybenzenesulfonic acid or as the isomer3-hydroxy-4-carboxybenzenesulfonic acid, or as a mixture thereof. Bothforms of the acid, which may commonly be prepared by the sulfonation ofsalicylic acid and which may as commercially available exist in the formof the dihydrate, may be represented by the formula I Os Is b JJOOHwherein a and b are each selected from the group consisting of O and 1and a+b=1. When a is 1 and b is 0, the formula becomes I and when a is 0and b is 1, the formula becomes II.

SOQH

SOsH

HO H0 30 OH 10 OH I II The compounds (R Sn) O which may be employed toform the novel products of this invention may include those wherein Rmay be a hydrocarbon radical which may be inertly substituted. Aninertly substituted hydrocarbon radical is one which contains no activegroups which may react with the other components of the reaction system.Typically R may be selected from the group consisting of alkyl, aryl,alkenyl, alkynyl, aralkyl, alkaryl, cycloalkyl, cycloalkenyl,cycloalkynyl, etc.

Typical alkyls may include methyl, ethyl, propyls, butyls, amyls,hexyls, heptyls, octyls, etc. Typical aryls may include phenyl,naphthyl, etc. Typical alkenyls may include vinyl, allyl, l-butenyl,etc. Typical alkynyls may include ethynyl, propynyls, butynyls, etc.Typical aralkyls may include benzyl, styryl, w-phenyl propyl, etc.Typical alkaryls may include tolyl, xylyl, etc. Typical cycloalkyls mayinclude cyclohexyl, cycloheptyl, methylcyclohexyls, etc. Typicalcycloalkenyls may include cyclohexenyl, cycloheptenyl, cyclohexadienyl,etc. It will be found that the nature of R will have little or no eifecton the process for preparing the compositions of this invention.

In one preferred embodiment, R may be a hydrocarbon radical selectedfrom the group consisting of lower alkyl radicals and the phenylradical.

It will be apparent to those skilled in the art that certain of thecompounds (R Sn) O may exist in equilibrium, in the presence of smallamounts of water, with the corresponding hydroxide viz.:

Furthermore, it will also be apparent that certain of the compounds (RSn) O may be prepared and commonly available (because of the aboveequilibrium) as the hydroxide, R SnOH. For example, the methyl, ethyl,and phenyl derivatives are commonly available as the hydroxide, e.g.triphenyltin hydroxide, rather than as the oxide. Thus, the formula (RSn) O may be taken to include the equivalent hydroxide R SnOH. Since theformer compound contains two R Sngroups per molecule and the lattercontains one, it will be necessary, when the hydroxide is used in placeof the oxide that the molar quantity of the tin compound be doubled sothat the same molar ratio of R Sn groups to sulfosalicylic acid will bemaintained.

Illustrative compounds (R Sn) O may include bis(trin-butyltin)oxide,bis(tri n amyltin)oxide, bis(tri nhexyltinjoxide, bis(tri npropyltin)oxide, bis(tri nocty1tin)oxide, trimethyltin hydroxide,triethyltin hydroxide, triphenyltin hydroxide, etc.

Preparation of the novel reaction products of this invention may beeffected by reacting sulfosalicylic acid with the compound (R Sn) O,Reaction of these compounds may be effected by mixing the reactants andheating the mixture preferably to at least about 100 C. and preferablyto 120180 C. at which temperature the water formed as by-product may :bevolatilized. The reaction mixture may be maintained at this temperaturefor at least about 30 minutes, and preferably 60-90 minutes. Reactionmay be conducted under vacuum if desired. During the course of thereaction in its preferred embodiment, as the evolved water isvolatilized, the mixture may become progressively more viscous until atthe end of 60-90 minutes, the mass may approach the solid state.

If desired, the reaction may be conducted at lower temperature and undermore readily controlled conditions by use of a diluent, preferably oneboiling above 100 C.l C. Preferably the diluent may (a) be a liquidwhich forms an azeotropic mixture with water, thereby driving thereaction .to completion, (b) be solvent for the product and (c) have aboiling point of about 110 C.200 C. Typical of the diluents which may beemployed may be toluene, xylenes, decalin, cymenes, cumene,ethylbenzene, t-butyl benzene, n-butyl ether, amyl alcohols, etc. Otherappropriate solvents including aliphatic or aromatic hydrocarbons,alcohols, ethers, etc. may be employed. When a diluent-solvent isemployed, e.g. benzene, the temperature of the reaction mixture may bee.g. 70 C. which may correspond to the boiling point of thebenzene-water azeotrope. In the practice of this invention, lowertemperatures may be employed but the reaction time will be greatlyincreased thereby.

When the reaction is conducted in the presence of diluent, it may beconducted under reflux until the theoretical amount of water isrecovered. The diluent may then be removed by distillation, preferablyat reduced pressure of typically -50 mm. Hg.

The desired reaction product may be formed in the reaction vessel as theby-product water is removed therefrom. As so prepared it may approach100% purity. It may be in the form of a liquid which on cooling maybecome a thick viscous liquid or pasty mass or a hard rock-like solid.

When the ratio of reactants is one mole of sulfosalicylic acid for 0.5mole of (R SN) O, the reaction may be as follows:

l C O OSnRs 4 This product may be isolated or if desired it may befurther reacted with an additional 0.5 mole of (R Sn) O as follows:

(BO 0 SIIR;

[S 0 811113] nHb [so snrmbm 1 M120 be 0811B; (2)

If desired, the sulfosalicylic acid may be reacted with an equimolaramount of (R Sn)- O to yield the last noted product,

The novel compositions of matter of this invention formed by thereaction of sulofsalicylic acid with a compound having the formula (RSn) 0 may have the formula 60 OSnR;

wherein R is a hydrocarbon radical; a, b, x and y are numbers eachindependently selected from the group consisting of 0 and l; a+b=l; andx+y=l.

It is a feature of this invention that the novel compounds, especiallythose containing R groups having less than about seven carbon atoms, areparticularly characterized by their unexpectedly high melting point.Typical of these preferred compounds may be noted those wherein R may bemethyl, ethyl, n-propyl, i-propyl, n-butyl, ibutyl, t-butyl, n-amyl,i-amyl, n-hexyl, i-hexyl, etc. In the preferred embodiment, R may be then-butyl radical. Another preferred compound may be that wherein R is then-propyl radical.

The novel products of this invention, and particularly the preferredproducts wherein R contains less than about seven carbon atoms, may becharacterized by their unexpectedly high melting point. The reactionproduct of either one mole or two moles of bis (tri-n-butyltin) oxideand two moles of sulfosalicylic acid for example melts above 260 C.; thecorresponding phenyl compound melts at about the same temperature. Thesecompounds are stable to temperatures which may approach 300 C. or

more.

Preparation of the novel products of this invention may be observed byinspection of the following examples wherein the parts are by weightunless otherwise indicated.

500 parts (2 moles) of sulfosalicylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 2500 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to 80 C. and 596 parts (1 mole) of his (tri-n-butyltin) oxideadded dropwise over thirty minutes. As the mixture is heated underreflux, water may be distilled out starting at about 93 C. Thetheoretical water, 90 parts (18 parts from the reaction proper and 72parts from the acid dihydrate), may be recovered as the toluene isdistilled off.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be slurried with petroleum ether, filtered,washed with petroleum ether, and air dried. Melting point may be above260 C.

The product upon cooling to room temperature may be found to have thefollowing analysis: Sn (percent): Calculated 23.3. Found 22.94. S(percent): Calculated 63. Found 6.77.

EXAMPLE 2 COOH -SO3H 179 parts (0.3 mole) of his (tri-n-butyltin) oxidemay be charged to an open reaction vessel. The oxide may then be heatedto 60 C. at which temperature 153 parts (0.6 mole) of sulfosalicylicacid dihydrate may be added with agitation. On heating with agitation,the mixture may begin to foam at about 95 C. As heating is eifected over30 minutes, the mass became completely liquid at 100 C. and as water wasboiled off, the mass became pasty as the temperature approached 115 C.after 60 minutes. The mass, which solidified on cooling to roomtemperature, was pulverized, slurried in petroleum ether, filtered,washed with water, filtered, washed with petroleum ether, and dried. Thedried solid product, obtained in amount of 294 parts, having a meltingpoint above 260 C., on analysis may be found to have substantially thesame analysis as the product of Example 1.

EXAMPLE 3 SO H -1 o)z n]2O H0- doorr SO:iSn(C4H l H2O HO- OOSI1 CAH9 3500 parts (2 moles) of sulfosalycylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 3000 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to 80 C. and 1192 parts (2 moles) of his (tri-n-butyltin)oxide added dropwise over thirty minutes. The mixture was heated underreflux. Water was distilled out starting at 93 C. The theoretical water108 parts (36 parts from the reaction proper and 72 parts from the aciddihydrate) may be recovered as the toluene is distilled off.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be washed with petroleum ether, filtered, andair dried. Melting point may be above 260 C.

EXAMPLE 4 so3n 2 1 sH )aS11]gO doorr -s0ur C O WaI-Ir);

500 parts (2 moles) of sulfosalycylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 1500 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to C. and 512 parts (1 mole) of his (tri-n-propyltin) oxideadded dropwise over thirty minutes. The mixture was heated under reflux.Water was distilled out starting at 93 C. The theoretical water parts(18 parts from the reaction proper and 72 parts from the acid dihydrate)may be recovered as the toluene is distilled Oh.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be washed with petroleum ether, filtered, andair dried. Melting point may be above 260 C.

500 parts (2 moles) of sulfosalicylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 2000 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to 80 C. and 716 parts (1 mole) of bis (tri-n-phenyltin) oxideadded dropwise over thirty minutes. The mixture was heated under reflux.Water was distilled out starting at 93 C. The theoretical water 90 parts(18 parts from the reaction proper and 72 parts from the acid dihydrate)may be recovered as the toluene is distilled 01?.

The product on cooling to room temperature may 'be found to be a whiterock-like solid. It may be washed with petroleum ether, filtered, andair dried. Melting point may be above 275 C.

500 parts (2 moles) of sulfosalicylic acid dihydrate may be charged to areactor fitted with stirrer, condenser, and thermometer. 2000 parts oftoluene may then be added and the mixture stirred for 10 minutes duringwhich time the acid may not go completely into solution. The mixture maybe heated to 80 C. and 932 parts (1 mole) of bis (tri-n-octyltin) oxideadded dropwise over thirty minutes. The mixture was heated under reflux.Water was distilled out starting at 93 C. The theoretical water 90 parts(18 parts from the reaction proper and 72 parts from the acid dihydrate)may be recovered as the toluene is distilled otf.

The product on cooling to room temperature may be found to be a whitepasty mass. It may be washed with petroleum ether, filtered, and airdried.

EXAMPLE 7 2 twtnm lz (I O OH ()0 OSn(C4Hv) 500 parts (2 moles) ofSulfosalicyclic acid dihydrate may be charged to a reactor fitted withstirrer, condenser, and thermometer. 2500 parts of toluene may then beadded and the mixture stirred for minutes during which time the acid maynot go completely into solution. The mixture may be heated to 80 C. and596 parts (1 mole) of his (tri-n-butyltin) oxide added dropwise overthirty minutes. As the mixture is heated under reflux, water may bedistilled out starting at about 93 C. The theoretical water, 90 parts(18 parts from the reaction proper and 72 parts from the aciddihydrate), may be recovered as the toluene is distilled ofl.

The product on cooling to room temperature may be found to be a whiterock-like solid. It may be slurried with petroleum ether, filtered,washed with petroleum ether, and air dried. Melting point may be above260 C.

It is a feature of the novel products of this invention that they areparticularly characterized by their high melting point especially whenthe R group contains less than about seven carbons. Because of thisfact, together with their extreme stability when subjected to hightemperature for extended periods of time, they may find use in hightemperature and/ or high pressure fluids.

It is also a feature of these novel compounds that they arecharacterized by their unexpected microbiological activity. It may bepossible to use these novel compounds to obtain sanitary material whichis substantially completely odor free. Because of the high melting andboiling by their extremely low vapor toxicity because of low vaportility, they may be retained on e.g. cloth or other textile for anextended period of time. They are characterized by theirextremely lowvapor toxicity because of low vapor pressure at ambient temperature.Such compounds, typically that formed by the process of Example 1, supramay be dissolved in volatile solvents such as methanol to form solutionwhich may be e.g. sprayed onto textiles or other surfaces which are tobe rendered resistant to attack by microorganisms for extended periodsof time.

To illustarte the microbiological action of these materials thefollowing experiments were carried out:

The products of Examples 1 (dissolved in ethanol), 3 (dissolved inethanol) and 4 (dissolved in methanol) were tested to determine theiranti-microbial activity by adding the solutions to each of a series ofstandard nutrient broths. I each series the broths after addition of thecompound contained 0.25, 0.5, 1, 2, 4, 8, 16, 32, and 64 parts permillion of the compound. The alcohol content of each broth was below theinhibitory amount. In each 8 series, the sample containing the minimumamount in parts per million (p.p.m.) which was elfective in controllingthe growth of the organism was noted and is tabulated below as theEffective Level, together with the organisms against which it wastested.

TableI.Tributyltin sulfosalicylate (Example 1) Effective Organism: levelp.p.m. Penicillium faniculosum 16 Aspergillus flavus 1 Candida albicans0.5 Bacillus mycoides 0.5

Table II.Bis (tri-n-butyltin) sulfosalicylate (Example 3) EffectiveOrganism: level p.p.m. Penicillium funiculosum Aspergillws flavus 0.5Candida albicans 0.25 Staph. aureus 1 Table III.Tripropyltinsulfosalicylate (Example 4) Effective Organism: level p.p.m. Penicilliumfuniculosum 2 Asp rgillus flavus 0.25 Candida albicans 0.25 Acrobacteracrogenes 31 Pseudomonas acruginosa 31 Staph. aureus 4 From inspectionof these tables, it will be apparent that these novel compositions arehighly active against various types tof organisms and that this activityis obtained by use of compounds which do not possess high volatility.Because of low volatility, the compounds may retain their activity insitu for extended periods of time. Furthermore these compounds, becauseof their low liquid solubility, are of considerably lower toxicity thanprior art compounds or than the intermediate oxides from which they maybe prepared. As as resul of the lower volatility, the vapor is low.

Although this invention has been described with reference to specificexamples, it will be apparent that various modifications may be madethereto which fall within the scope of this invention.

1 claim:

1. The method for controlling the growth of microorganisms selected fromthe group consisting of bacteria and fungi which comprises applying tothe locus at which control is desired an etfective amount of a compoundof the formula U 0 OSnRs wherein R is a hydrocarbon selected from thegroup consisting of lower alkyl and phenyl; a, b, x, and y, are selectedfrom the group consisting of 0 and 1; a+b=1; and x+y:1.

2. The method for controlling the growth of microorganisms as claimed inclaim 1 wherein R is n-butyl.

3. The method for controlling the growth of microorganisms as claimed inclaim 1 wherein R is n-propyl.

9 4. The method for controlling the growth of microorganisms selectedfrom the group consisting of bacteria and fungi which comprises applyingto the locus at which control is desired an efiective amount of acompound of the formula C O OSuR;

wherein R is a hydrocarbon selected from the group consisting of loweralkyl and phenyl; x and y are selected from the group consisting of and1; and x+y=1.

5. The method for controlling the growth of microorganisms as claimed inclaim 4 wherein R is n-butyl.

6. The method for controlling the growth of microorganisms as claimed inclaim 4 wherein R is n-propyl.

7. The method for controlling the growth of microorganisms as claimed inclaim 4 wherein y: 1.

h. The method for controlling the growth of microorganisms selected fromthe group consisting of bacteria 10 and fungi which comprises applyingto the locus at which control is desired an effective amount of acompound of the formula S|O3(S11R3)x y G O OS11R wherein R is ahydrocarbon selected from the group consisting of lower alkyl andphenyl; x and y are selected from the group consisting of 0 and 1; andx+y=1.

9. The method for controlling the growth of microorganisms as claimed inclaim 8 wherein R is n-butyl.

10. The method for controlling the growth of microorganisms as claimedin claim 8 wherein R is n-propyl.

11. The method for controlling the growth of microorganisms as claimedin claim 8 wherein 1:1.

References Cited UNITED STATES PATENTS 3,201,432 8/1965 Leebrick260-429.7

ALBERT T. MEYERS, Primary Examiner J. D. GOLDBERG, Assistant Examiner

